Wang Huawei, Ye Yujia, Wan Wen, Wang Luqiao, Li Ruijie, Li Longjun, Yang Lihong, Yang Lai, Gu Yajuan, Dong Ling, Meng Zhaohui
Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Pharmacol. 2019 Aug 23;10:923. doi: 10.3389/fphar.2019.00923. eCollection 2019.
Xinmailong (XML), a bioactive composite extracted from , has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet and antithrombotic effects. The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed using an acute pulmonary thrombosis mouse model. XML dose-dependently inhibited platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model. Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.
心脉隆(XML)是一种从……中提取的生物活性复合物,已被广泛用于治疗充血性心力衰竭等心血管疾病。然而,XML是否具有抗血小板和抗血栓作用尚不清楚。评估了XML对激动剂诱导的血小板聚集、黏附与铺展、颗粒分泌、整合素αIIbβ3激活以及血栓形成的影响。还研究了XML对激动剂诱导的血小板中Syk、PLCγ2、Akt、GSK3β和MAPK信号分子磷酸化的影响。此外,使用急性肺血栓小鼠模型观察了XML的抗血栓作用。XML剂量依赖性地抑制凝血酶、胶原蛋白和花生四烯酸(AA)诱导的血小板聚集和颗粒分泌。XML还显著减少了血小板在胶原蛋白和纤维蛋白原包被表面的黏附与铺展。生化分析表明,XML抑制凝血酶、胶原蛋白和AA诱导的Syk、PLCγ2、Akt、GSK3β和MAPK磷酸化。此外,在胶原蛋白-肾上腺素诱导的急性肺血栓小鼠模型中,XML显著抑制血栓形成。在此,我们首次报道表明XML抑制血小板功能并具有抗血栓活性。这表明XML可能是预防或治疗血小板相关心血管疾病的潜在治疗候选物。